SCN5A H558R - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

SCN5A H558R

(SCN5A His558Arg)


Short summary

 

Variant evidence
Computational 1

PolyPhen-2 predicts SCN5A-H558R to be BENIGN with a score of 0.000 (sensitivity: 1.00; specificity: 0.00).

Functional -
Case/Control 2

In this study, the entire SCN5A coding region is sequenced in 375 subjects with atrial fibrillation or atrial fibrillation associated with heart disease. Controls (n=360) from the same population were then genotyped to identify all variants identified in the study subjects. The frequency of the common variant SCN5A-H558R was 189/752 in the cases and 128/720 in the controls (p = 0.006326980543447317).

See Darbar D et al. 2008 (18378609).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr3:38645420: 24.6% (2542/10350) in EVS
  • C @ chr3:38620423: 21.1% (27/128) in GET-Evidence
  • Frequency shown in summary reports: 24.6% (2542/10350)

Publications
 

Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008 Apr 15;117(15):1927-35. doi: 10.1161/CIRCULATIONAHA.107.757955. Epub 2008 Mar 31. PubMed PMID: 18378609; PubMed Central PMCID: PMC2365761.

In this study, the entire SCN5A coding region is sequenced in 375 subjects with atrial fibrillation or atrial fibrillation associated with heart disease. Controls (n=360) from the same population were then genotyped to identify all variants identified in the study subjects. The frequency of the common variant SCN5A-H558R was 189/752 in the cases and 128/720 in the controls (p = 0.006326980543447317).

Shinlapawittayatorn K, Du XX, Liu H, Ficker E, Kaufman ES, Deschênes I. A common SCN5A polymorphism modulates the biophysical defects of SCN5A mutations. Heart Rhythm. 2011 Mar;8(3):455-62. Epub 2010 Nov 23. PubMed PMID: 21109022; PubMed Central PMCID: PMC3050092.

 

Chen L, Zhang W, Fang C, Jiang S, Shu C, Cheng H, Li F, Li H. Polymorphism H558R in the human cardiac sodium channel SCN5A gene is associated with atrial fibrillation. J Int Med Res. 2011;39(5):1908-16. PubMed PMID: 22117993.

 

Genomes
 

 

 

 

 

 

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom C @ chr3:38645420

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr3:38645420

 

 

 

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr3:38645420

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het C @ chr3:38645420

 

GS06994 - var-GS06994-1100-36-ASM
het C @ chr3:38620424

 

GS18504 - var-GS18504-1100-36-ASM
het C @ chr3:38620424

 

GS18505 - var-GS18505-1100-36-ASM
het C @ chr3:38620424

 

GS19020 - var-GS19020-1100-36-ASM
het C @ chr3:38620424

 

GS19025 - var-GS19025-1100-36-ASM
het C @ chr3:38620424

 

GS19026 - var-GS19026-1100-36-ASM
het C @ chr3:38620424

 

GS19129 - var-GS19129-1100-36-ASM
het C @ chr3:38620424

 

GS19648 - var-GS19648-1100-36-ASM
het C @ chr3:38620424

 

GS19649 - var-GS19649-1100-36-ASM
het C @ chr3:38620424

 

GS19669 - var-GS19669-1100-36-ASM
het C @ chr3:38620424

 

GS19700 - var-GS19700-1100-36-ASM
het C @ chr3:38620424

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr3:38620424

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr3:38620424

 

GS20502 - var-GS20502-1100-36-ASM
het C @ chr3:38620424

 

GS21767 - var-GS21767-1100-36-ASM
het C @ chr3:38620424

 

Other external references
 

    dbSNP
  • rs1805124
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the SCN5A gene
    Dilated Cardiomyopathy
    Brugada Syndrome
    Long QT Syndrome 3
    LQT3-Related Romano Ward Syndrome
    Progressive Cardiac Conduction Disease
    Romano-Ward Syndrome
    SCN5A-Associated Dilated Cardiomyopathy
    SCN5A-Related Dilated Cardiomyopathy
    SCN5A-Related Disorders
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN5A
    PharmGKB
  • [Long QT Syndrome]
    Has been studied in association with long QT.
    www.pharmgkb.org/search/annotatedGene/scn5a/

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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